Effect Of IPC Research Articles

Effect of an Oral Iron(III)-hydroxide Polymaltose Complex on Tetracycline Pharmacokinetics in Patients with Iron Deficiency Anemia

The study was carried out as an open-label, but laboratory-blind, single-dose, single-centre, randomized, two-period crossover study. Twenty-two patients with iron deficiency anemia completed the study. The study consisted of two treatment phases of 36 h, separated by a washout period of between 6 and 14 days. The two treatments were given orally. The reference treatment was tetracycline (CAS 60-54-8) alone (2 x 250 mg capsules) and the test treatment was iron(III)-hydroxide polymaltose complex (IPC, Maltofer) together with tetracycline (2 x 250 mg capsules). IPC had no pharmacokinetic effect on the rate of absorption of tetracycline. With concomitant administration of tetracycline and IPC sufficiently high tetracycline concentrations, to ensure bacteriostasis, will be reached. An inhibitor effect of IPC to the tetracycline absorption, as it is known for ferrous salts, could not be observed.

Increased myocardial substrate uptake contributes to the protection of ischemic preconditioning: role of insulin-dependent Akt and AMPK activation

IntroductionSwitched myocardial substrate uptake from fatty acids to carbohydrate has been proposed to resist ischemia/reperfusion injury. We hypothesised that altered myocardial substrate uptake during early reperfusion may contribute to IPC-afforded...

124. Mitochondrial Respiratory Complex I and II Activities are Preserved by Ischemic Preconditioning

Mitochondrial respiratory complexes are damaged by ischemia reperfusion injury. While IPC preserves overall mitochondrial respiratory function after ischemia reperfusion, it is unclear which is the effect of IPC on individual mitochondria respiratory complexes. The purpose of this experiment was to determine the effect of IPC on mitochondrial respiratory complexes. Isolated rat hearts (n=6/group) were subjected to either A) 40 minutes (min) of equilibration (EQ), 30 min of ischemia (I), and 30 min of reperfusion (RP) (CONTROL) or B) 10 min of EQ, three 5 min episodes of IPC, 30 min I, and 30 min of RP (IPC group).

Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: involvement of mitochondrial KATP channels and reactive oxygen species

Ischemic preconditioning (I-PC) induced by brief episodes of ischemia and reperfusion (I/R) protects the heart against sustained I/R. Although activation of mitochondrial K(ATP) channels (mitoK(ATP)) interacting with reactive oxygen species (ROS) has been proposed as a key event in this process, their role in the antiarrhythmic effect is not clear. This study was designed: 1) to investigate the involvement of mito K(ATP) opening in the effect of I-PC (1 cycle of I/R, 5 min each) on ventricular arrhythmias during test ischemia (TI, 30-min LAD coronary artery occlusion) in Langendorff-perfused rat hearts and subsequent postischemic contractile dysfunction, and 2) to characterize potential mechanisms of protection conferred by I-PC and pharmacological PC induced by mito K(ATP) opener diazoxide (DZX), with particular regards to the modulation of ROS generation. Lipid peroxidation (an indicator of increased ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in non-ischemic controls, non-preconditioned and preconditioned hearts exposed to TI, I-PC alone, as well as after pretreatment with DZX, mito K(ATP) blocker 5-hydroxydecanoate (5-HD) and antioxidant N-acetylcysteine (NAC). Total number of ventricular premature beats (VPB) that occurred in the control hearts (518+/-71) was significantly (P<0.05) reduced by I-PC (195+/-40), NAC (290+/-56) and DZX (168+/-22). I-PC and NAC suppressed an increase in CD and TBARS caused by ischemia indicating lower production of ROS. On the other hand, I-PC and DZX themselves moderately enhanced ROS generation, prior to TI. Bracketing of I-PC with 5-HD suppressed both, ROS production during PC and its cardioprotective effect. In conclusion, potential mechanisms of protection conferred by mito K(ATP) opening in the rat heart might involve a temporal increase in ROS production in the preconditioning phase triggering changes in the pro/antioxidant balance in the myocardium and attenuating ROS production during subsequent prolonged ischemia.

Ischemic preconditioning suppresses apoptosis of rabbit spinal neurocytes by inhibiting ASK1–14-3-3 dissociation

The mechanism by which a brief episode of sublethal ischemia followed by reperfusion (ischemic preconditioning, IPC) prevents the lethal effects of subsequent periods of prolonged ischemia, are poorly understood. A completely randomized, controlled study was designed to study the effect of IPC using a rabbit model of ischemic spinal cord injury. Twenty-four white adult New England rabbits were randomly assigned to one of 3 groups (n=8 per group); the groups were assigned as follows: Group I: sham-operation group, Group II: ischemic reperfusion (I/R) group, and Group III: ischemic preconditioning group. Spinal cord ischemia was induced by introducing an infra renal aortic cross-clamp for 30min. Following injury, rabbits were subjected to 30min, 2h, or 8h of reperfusion in Group II. In Group III, subjects underwent three cycles, 5min each, of ischemia followed by 5min of reperfusion, before receiving 30min of ischemia. We previously reported that the association between ASK1 (apoptosis signal-regulating kinase 1) and 14-3-3 played an important role in regulating ischemia/reperfusion spinal cord injuries. To evaluate the effect of ischemic preconditioning in injured spinal cords, we examined alterations in spinal tissue morphology, activation of key members of the ASK1-mediated signaling pathway, and the association between ASK1 and 14-3-3. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. The phosphorylation levels of ASK1, JNK, and p38 were assessed by immunoblot analysis. The association between ASK1 and 14-3-3 was analyzed by co-immunoprecipitation experiments. We observed that swelling of the neurocyte bodies and hemorrhage of the spinal cord were dramatically decreased in Group III compared to Group II. In addition, the degree of apoptosis among neurocytes was reduced in Group III compared to Group II. Finally, the phosphorylation of ASK1, JNK, p38 and the dissociation of ASK1 from 14-3-3 were dramatically decreased in Group III compared with Group II. These results indicate that ischemic preconditioning may have a protective affect against ASK1/14-3-3 dissociation-induced spinal cord injuries.

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation

Abstract Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n= 7) received grafts without IPC, group Tx&IPC received grafts with IPC. Animals that had not undergone transplantation but whose pancreata had been exteriorized served as controls (n= 5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4°C. IPC was induced by interruption of the arterial blood flow for 10 min followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation (P<0.01). In parallel, AI was significantly increased in transplanted grafts compared to the controls (P<0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in AI (P<0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation.

Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n=7) received grafts without IPC, group Tx&IPC received grafts with IPC. Animals that had not undergone transplantation but whose pancreata had been exteriorized served as controls (n=5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4 degrees C. IPC was induced by interruption of the arterial blood flow for 10 min followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation ( P<0.01). In parallel, AI was significantly increased in transplanted grafts compared to the controls ( P<0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in AI ( P<0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.

Role of Adenosine in Renal Protection Induced by a Brief Episode of Ischemic Preconditioning in Rats

The protective effect of a brief episode of ischemic preconditioning was examined at an early phase of ischemic-reperfusion injury in the rat kidney. Rats were subjected to 50 min of left renal artery occlusion followed by 120 min of reperfusion. Ischemic preconditioned rats were subjected to preconditioning with two cycles of 3-min ischemia and 5-min reperfusion (IPC). Ischemic-reperfusion injury led to a low recovery of the glomerular filtration rate (GFR). Overt morphological changes, consisting of blood trapping and tubular collapse, were seen. IPC improved the recovery of GFR and renal morphology. The IPC effect was not blocked by 8-(p-sulfophenyl)-theophylline (SPT), a non-selective adenosine receptor antagonist, by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1-receptor antagonist, or by 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2-receptor antagonist. Intravenous infusion of adenosine (30 μg/min per rat, for 5 min) prior to the 50-min occlusion improved the recovery of GFR, and this protection of GFR was blocked by SPT. Thus, both IPC and exogenous adenosine attenuated ischemic-reperfusion injury of the kidney. However, because three adenosine receptor antagonists failed to abolish the protective effect of IPC, there is no evidence to indicate that activation of adenosine receptors contributes to the IPC effect in the kidney.

Effect of Preconditioning by Low-Flow Perfusion on Cardioprotection

Background and Objectives:Recent reports suggest that brief periods of low-flow ischemia (lf Isc and reperfusion (R before prolonged Isc mimic ischemic preconditioning (IPC in murine hearts, probably by a preservation of high energy phosphates. Materials and Methods:In order to test this hypothesis, Langendorff- perfused isolated rabbit hearts were subjected to 45 min lf Isc (5% of baseline perfusion flow with lf IPC or not, followed by 120 min R. lf IPC was induced by a single episode of 5 min lf Isc and 10 min R. These were compared with IPC hearts by 5 min no-flow Isc and 10 min R. Results:lf IPC as well as IPC enhanced post- ischemic functional recovery although IPC did not reduce infarct size (Isc control, 37.5±3.1, IPC, 16.2±1.5, lf Isc, 43.0±0.7, and lf IPC, 40.4±1.0% of the left ventricle. Myocardial ATP hydrolysis and lactate prod- uction during the preischemic, ischemic, and reperfusion periods were not differ between the experimental groups. Conclusion:These results suggest that a brief period of lf Isc could not precondition the rabbit heart and the energy metabolism hypothesis may not be a universal mechanism for the cardioprotective effect of IPC. (Korean Circulation J 2001;31( ( ( (12 :1252-1260

Ischemic preconditioning attenuates postischemic leukocyte adhesion and emigration.

Intravital microscopy was used to determine whether ischemic preconditioning (IPC; 5 min ischemia and 10 min reperfusion) would attenuate leukocyte adhesion and emigration induced by subsequent prolonged ischemia (60 min) and reperfusion (60 min) (I/R) in murine cremaster muscle and whether adenosine produced during IPC and/or reperfusion contributed to these beneficial effects. I/R elicited a marked increase in the number of adherent and emigrated leukocytes compared with the nonischemic control muscles, an effect that was largely prevented by IPC. Superfusion of the cremaster with adenosine deaminase only during IPC or only during 60-min reperfusion attenuated the inhibitory effect of IPC on postischemic leukocyte adhesion and emigration. However, the beneficial effects of IPC were mimicked in cremaster muscles preconditioned with adenosine (topical application for 10 min beginning 20 min before the onset of prolonged ischemia). Similar results were obtained in experiments in which adenosine was topically applied to the cremaster only during the 60-min reperfusion period. Our findings suggest that the ability of IPC to attenuate postischemic leukocyte adhesion and emigration may be mediated by adenosine released during IPC and during reperfusion after prolonged ischemia.

Ischemic preconditioning improves cardiac functional recovery following preservation with University of Wisconsin solution.

Single or multiple brief periods of regional or global ischemia and reperfusion prior to a prolonged ischemic insult showed cardioprotective effects. Although this phenomenon (ischemic preconditioning [IPC]) has been described in ischemic reperfusion models, the effect of IPC on heart preservation has not been previously reported. We, thus, investigated the effect of IPC on heart preservation. Hearts isolated from male Wistar rats (250-350 g) were mounted on a Langendorff apparatus to estimate baseline function (aortic flow, coronary flow, cardiac output, heart rate, systolic pressure, and rate pressure product). All hearts were divided into 5 groups. In groups 1 and 4, the hearts were subjected to 8 and 12 hr of preservation, respectively. The hearts in group 2 were subjected to a single 2.5-minute cycle of normothermic global ischemic episode (IPC) before 8 hr of preservation. In groups 3 and 5, the hearts were subjected to two 2.5-min IPC cycles and stored for 8 or 12 hr. The hearts were arrested with University of Wisconsin solution and stored at 4 degrees C. Following storage, the hearts were reperfused and measured postpreservative function to assess cardiac functional recovery. Lactate and troponin-T leakage in the coronary perfusate was also measured. In group 3, the treatment of two 2.5-min IPC cycles significantly increased cardiac output, but the treatment of single 2.5-min IPC cycle did not affect the result. In the extended preservation group (group 5), the recovery (%) of both coronary flow and cardiac output were significantly increased compared with group 4. Furthermore, lactate leakage was significantly reduced in groups 2 and 3. These results suggest that IPC improves cardiac functional recovery following simple cold storage and has cardioprotective effects in rat heart preservation.

Effect of IPC on Selections of Wild Oats

Effect of IPC on Selections of Wild Oats